We will be collaborating with centers which are generating genetic expression data on both human tumors and normal tissues to seek candidate proteins suitable for immune attack. Using gene expression data, we are searching for antigens over-expressed on tumors and not expressed by important or essential normal tissues. Then the plan is to either identify and clone TCRs in patients with tumors expressing these targets or generate TCRs in HLA-transgenic mice. Chimeric antigen receptors will also be developed if the antigens are cell surface-expressed. Thusfar, we have succeeded in generating and optimizing a chimeric antigen receptor targeting CD70, a protein on nearly all human renal cancer, thymic cancers and many blood cancers and an approved protocol is enrolling.